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Summer/Fall 2017 Issue II The Global Alzheimer’s Association Interactive Network Newsletter

WELCOME BACK From GAAIN’s PI, Arthur W. Toga

IN THIS ISSUE: NEW & IMPROVED With GAAIN’s new Interrogator tool, users can explore, query and visualize data with unprecedented power. GAAINING TRACTION GAAIN demoed its pioneering data sharing technology and recruited new Data Partners at the 2017 Alzheimer’s Association International Conference. GROUNDBREAKING STUDY A new study published in the August issue of JAMA Neurology used GAAIN data to reexamine the link between age, gender, and Alzheimer’s risk. DATA PARTNERS SPOTLIGHT GAAIN would like to extend a warm welcome to our new Data Partners. GAAIN SYSTEM TOOLS TUTORIAL SERIES

he GAAIN team is thrilled to announce the launch of our new and greatly improved Interrogator tool, which I am confident will significantly enhance the role of big data in dementia science. Over the past year, GAAIN has made remarkable progress in several areas: growing our pool of data, forging new partnerships, and educating our fellow researchers on the power of GAAIN. We led data sharing efforts at the Alzheimer’s Association International Conference and published key results based on GAAIN data. Most exciting of all, our work is just beginning. With passion and purpose, we look forward to more collaborations, bigger data, and ongoing breakthroughs in the field of Alzheimer’s research. We invite you to join us on this path. With Regards,

Tutorials are now available on our YouTube page to help users navigate GAAIN tools. NEW: GAAIN TEAM MEMBER Meet Jyl Boline, Project Specialist for GAAIN. GAAIN FAQs Learn more about how GAAIN can enhance your current research.

Arthur W. Toga Principal Investigator, GAAIN Director, Laboratory of Neuro Imaging Director, USC Mark and Mary Stevens Neuroimaging and Informatics Institute

NEW & IMPROVED: GAAIN’S INTERROGATOR TOOL

The

Explore, query, and visualize Alzheimer’s data with EDSA DATASET DATASET unprecedented power using GAAIN’s new InterrogatorNACC tool! 1,744 474 35,768 AIBL DATASET

The Australian Imaging Biomarkers & Lifestyle Flagship Study of Ageing

APPLY

MMSE_TOT Sex APOE Diagnosis Age

APPLY

GAAIN was driven to develop the improved + Interrogator to aid researchers in their quest to access quality Alzheimer’s data. Many datasets are largely unknown to the wider research community, while others are promI-ADNI DATASET inent but require significant282effort Italian to access. Alzheimer’s SELECT

AIBL DATASET 1,744

APPLY

SELECT

474

282

APPLY

SELECT

EDSD, ADNI, NACC

3 PARTNERS

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2,983

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Add Variable

(39,225 SUBJECTS)

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39,225 EDSD, ADNI, NACC

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indicator

Has APOE 3-3 Has APOE 3-4 Has APOE 4-4

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Control Cohort Normal Females

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Case Cohort Females with AD

Indicator or numerical variable

indicator Has APOE 4-4

Age

Females Clear

My Cohorts (8) My Analyses (0)

MMSE Sex APOE Diagnosis Has APOE 2-2 Has APOE 2-3 Has APOE 2-4

Create custom X cohorts with drag Normal Females and drop

Case Cohort

Variable

Has APOE 3-4 Share results with colleagues

Run Analysis

Indicator or numerical variable

Females with AD

Indicator or numerical variable

This tool is intended to assist Clear Run Analysis researchers in testing preliminary hypotheses as they design new research studies. Those who wish to conduct a full analysis based on their initial findings will then connect directly with Data Partners. GAAIN’s ultimate goal is to connect its users with Data Partners to form new partnerships and accelerate research on Alzheimer’s disease and related dementias. Females

Analysis Type

Has APOE 2-3

(39,225 SUBJECTS)

Control Cohort

POOLED DATASET

Logic Regression

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POOLED DATA

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National Alzheimer’s Coordinating Center

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151

PHARMACOG DATASET

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Alzheimer’s Disease Repository Without Borders

PHARMACOG DATASET

APPLY

Although still in beta, the new Interrogator will ultimately afford access to information + about more than 470,000 subjects from our 30 Data Partners (this version currently APPLY APPLY APPLY contains datasets from eight Data Partners). Users interested in testing the new tool Harmonized Variables (11) Conduct SET UP are encouraged to apply for access. Meanwhile, GAAIN team members Add VariableMMSE preliminary ANALYSIS Sex are working to migrate Data analyses with APOE Partners to the new platform. remotely SELECT

2,819

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SELECT

SELE

ARWIBO DATASET

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Disease Neuroimaging Initiative

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Diagnosis

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Explore Big Data

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The Interrogator Explore Big Data Summer/Fall 2017 Issue II

Harmonize Variables Name the variable 39,225

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National Alzheimer’s Coordinating Center

to quickly and easily define their own groups of subjects and do preliminary analyses to test their HARMONIZE hypotheses,” said Scott Neu, the GAAIN team member in charge of developing the new interface. “Harmonization processes which once took three to four days now take just three to four minutes.”

35,768

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“The new tool is highly flexible, allowing users

35,768

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3.0 2.8

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2.0 1.8

1.6 1.4

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Variables

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Odds Ratios

P Value

Age

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avg = 74.09

avg = 71.72

1.05 (1.05 to 1.06)

P<0.001

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avg = 73.87

avg = 71.99

1. 04 (1.04 to 1.05)

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Has APOE 3-4

Females

n = 1,382

n = 1,515

2.43 (2.22 to 2.66)

P<0.001

Males

n = 1,098

n = 1,033

2.35 (2.12 to 2.60)

P<0.001

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n = 457

n = 186

7.66 (6.39 to 9.19)

P<0.001

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n = 426

n = 125

8.23 (6.67 to 10.2)

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n = 1,939

n = 1,701

Has APOE 4-4

GET INVOLVED Subjects:

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For statistical analyses, logistic regression, linear regression, Mantel-Haenszel meta-analysis, and Cox proportional hazard numerical Age regression are all supported.

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4,000

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Another key function of the updated Interrogator is its improved Subjects data pooling and harmonization capabilities. Researchers whoSubjects have previously performed these tasks by hand can now use an intuitive interface to quickly combine datasets.

Odds Ratio

MAPPING

SET UP

COHORT

Sex

Age

Map

COHORT

Cases

Males = 1,524 n = 1,158 GAAIN is seeking beta testers for the newn Interrogator, especially users experienced with logistic and Cox proportional hazard regression. Apply now by visiting gaaindata.org or emailing info@gaain.org.

GAAINING TRACTION AT THE 2017 ALZHEIMER’S ASSOCIATION INTERNATIONAL CONFERENCE

Researchers from around the world converged in London, England in July for the Alzheimer’s Association International Conference (AAIC). More than 5,600 researchers, clinicians, and members of the care community attended the global forum aimed at advancing dementia science. To illustrate the power and potential of data sharing efforts in Alzheimer’s research, GAAIN principal investigator Arthur W. Toga led a symposium alongside Pieter Jelle Visser of the European Medical Information Framework (EMIF). The session featured several prominent data-sharing platforms—GAAIN, EMIF, Dementia Platform United Kingdom (DPUK), and the European Prevention of Alzheimer’s Dementia (EPAD) Registry—with the goal of increasing exposure and encouraging AAIC attendee participation. Of these initiatives, GAAIN is the only immediately accessible, open-access platform. GAAIN operated a booth at the conference, welcoming an estimated 400 visitors. Visitors included current Data Partners, clinicians, researchers interested in joining GAAIN as a Data Partner or user, and representatives from the Alzheimer’s activist and outreach communities. Members of the GAAIN team performed hundreds of live demos of the new Interrogator, which garnered significant positive feedback and attention. GAAIN’s presence at the conference was a terrific opportunity to promote the platform’s visibility, enable targeted recruitment efforts, and open avenues to new partnerships in multiple capacities. Post-AAIC priorities include reconnecting with potential new users and Data Partners, as well as migrating data to the new Interrogator for public use as quickly as possible. Next year, the team plans to hold a GAAIN-specific user workshop at AAIC.

Summer/Fall 2017 Issue II

GROUNDBREAKING GAAIN STUDY REDEFINES LINK BETWEEN AGE, GENDER, AND ALZHEIMER’S RISK The study, “Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease,” published in the Journal of the American Medical Association (JAMA) Neurology on August 28, overturned long-held beliefs about who is at greatest risk for Alzheimer’s disease. Genetically vulnerable white men and women—those with one copy of the ApoE4 gene variant—have the same odds of developing the disease between the ages of 55 and 85, with one exception. From their mid-60s to mid-70s, women have a significantly higher risk. The new results provide a more nuanced understanding of how gender modifies Alzheimer’s risk. Until now, researchers relied heavily on the results of a 20-year-old study, which suggested that women with one copy of ApoE4 were diagnosed with the disease 50 percent more than men with the same genetic profile, across age groups. “So much work has been dependent on one 1997 finding, but with tools like GAAIN, we now have the ability to reinvestigate with increased statistical power,” said Arthur W. Toga, GAAIN principal investigator and director of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (INI). INI Assistant Professors Judy Pa and Scott Neu, co-authors of the study, hope their work will help researchers better understand the pathology of Alzheimer’s disease. For example, the disease may present differently in men and women based on hormones or other factors. Ultimately, intervention studies may be designed in response to the variable risk identified here. GAAIN data fueled the analysis, which included 57,979 North American and European subjects. The network promotes large-scale data-sharing through its federated approach to the analysis of metadata. “GAAIN’s goal, as illustrated by this study, is to connect scientists with those who have collected data in order to create new collaborations to further research and understanding of Alzheimer’s disease,” said Neu.

Contributing Data Partners included: Alzheimer’s Disease Neuroimaging Initiative (ADNI) Alzheimer’s Disease Repository Without Borders (ARWIBO) Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing (AIBL) Barcelona Alzheimer’s Treatment and Research Center (ACE) Coalition Against Major Diseases (CAMD) European Diffusion Tensor Imaging Study in Dementia (EDSD)

Framingham Heart Study (FHS) Laboratory of Magnetic Resonance Research (LMRR) National Alzheimer’s Coordinating Center (NACC) NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) PharmaCog Wisconsin Registry for Alzheimer’s Prevention (WRAP)

“Most of the archives around the world have insufficient numbers of underrepresented groups. One of the take-home messages from our study is people of all races and ethnicities need to be involved in Alzheimer’s clinical trials because this disease is a problem that affects all of us.” – Arthur W. Toga 5

DATA PARTNER SPOTLIGHT GAAIN would like to extend a warm welcome to our new Data Partners. Brain Health Registry is a large-scale longitudinal initiative at the University of California San Francisco to monitor brain health over time to contribute to research on Alzheimer’s disease, Parkinson’s disease, depression, PTSD and other disorders. DES C R IPA

Descripa is a European collaborative study that aims to develop screening guidelines and clinical criteria for Alzheimer’s disease in pre-dementia patients. The Sydney Memory and Ageing Study, Centre for Healthy Brain Ageing (CHeBA) investigates the clinical characteristics of MCI to determine age-related change in cognitive function. Participants were non-demented at baseline. Longitudinal data is collected using neuropsychological tests, medical assessments, blood samples, MRI, and self-reported data. AddNeruoMed is part of the Innovative Medicines Initiative, Europe’s largest public-private biomedical research collaboration. The study aims to find a biomarker for Alzheimer’s disease. Vienna Transdanube Aging Study (VITA) is a population-based cohort study of all 606 75-year-olds within a specific region of Vienna. The primary focus of the VITA work group, which follows participants for 4 years, is to establish a prospective age cohort for evaluation of prognostic criteria for the development of Alzheimer’s.

MAKE THE MOVE TO GAAIN’S NEW INTERROGATOR Calling all Data Partners: it’s time to switch over to our new Interrogator interface. Please contact GAAIN for details.

Explore more information than ever before. Our growing list of Data Partners, now 30, allows users to explore information related to more than 470,000 subjects with approximately 2,100 data attributes from around the globe. Connect with other researchers working toward a common goal. In the coming months, GAAIN will release Launch Pages featuring additional information about each Data Partner and its available datasets. Launch Pages will also outline steps to forge collaborative relationships with Data Partners beyond the tools GAAIN offers. Stay tuned for updates.

Summer/Fall 2017 Issue II

GAAIN In the News An international team of researchers from the UK, Spain and Sweden formed the TriBEKa Consortium and launched an Alzheimer’s imaging study. They will share the data they collect via GAAIN. Read more in the Pharma Times.

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NEW: GAAIN SYSTEM TOOLS TUTORIAL SERIES Need assistance with our tools? Tutorials are available on the GAAIN YouTube channel to help users navigate the following platforms: Introduction to Data Landing Page See how to navigate the home page and learn more about our Data Partners. GAAIN Scoreboard Find out how to use this interactive interface, which helps researchers quickly discover Data Partners with datasets that match their interests.

SCOREBOARD



GAAIN Cohort Scout Learn about our interactive Cohort Scout, which enables users to create unique cohorts. Users can search through thousands of subject-level attributes and build, save, and share their own custom cohorts. GAAIN Interrogator Discover how to use the GAAIN Interrogator, an interactive tool that researchers can use to conduct preliminary analysis across multiple Data Partner datasets and visualize the results.

COHORT SCOUT



NEW: GAAIN TEAM MEMBER Meet Jyl Boline, Project Specialist for GAAIN, who joined the team in March 2017. She received her Ph.D. from the University of Minnesota before completing a Sloan Postdoctoral fellowship at the California Institute of Technology. Over the past 12 years, Boline’s work has focused on collaborative neuroinformatics, including the Bioinformatics Research Network at LONI, the International Neuroinformatics Coordinating Facility at the Karolinska Institute, and the Human Brain Project. In her role with GAAIN, her responsibilities include outreach, expansion of the GAAIN network, and regularly interfacing with Data Partners and users. She will also assist GAAIN with building relationships with stakeholders and sponsors, strategic planning and establishment of internal operations protocols, robust and manageable expansion of the GAAIN network, and communications and public relations. 7

FREQUENTLY ASKED QUESTIONS Learn more about how GAAIN can enhance your current research. What is the primary function of GAAIN? GAAIN is an open-access federated data discovery platform. Its goal is to connect Alzheimer’s disease researchers to data, fostering cohort discovery and collaboration in the process. Users (researchers looking for data to guide their analyses) can interface directly with Data Partners (research groups actively collecting data) to build productive and exciting collaborations. What type of data can I explore with GAAIN? GAAIN’s new Interrogator tool provides information about thousands of attributes, including genetic, imaging, clinical, behavioral and others. For example: • Demographics: age, sex, country, ethnicity, race, handedness • Cognitive assessments: MMSE, CDR, LIMM, LDEL, and others • Health factors: diagnosis, ApoE, family history, behavioral history • Biologics: plasma, CSF • Imaging: MRI, PET, CT, SPECT • Genetics: genotypes, WGS Who is eligible to become a GAAIN Data Partner and how can I apply? Data Partners include studies, clinics and consortiums that have collected data on subjects with Alzheimer’s disease or the aging brain and are interested in accelerating research on causes, diagnosis, treatment, and prevention. Data Partners maintain complete control over the data they choose to share with GAAIN. To start the process, fill out the GAAIN Partner Application or learn more on the Partners section and apply via our website. You can also contact us at info@gaain.org. What kind of analyses can I perform with GAAIN? The new GAAIN Interrogator tool allows users to conduct preliminary analyses with remotely accessible data from thousands of subjects. Data pooling and harmonization features are built into the tool, and the following analyses are supported: logistic regression, linear regression, Mantel-Haenszel meta-analysis, and Cox proportional hazard regression. How do I access GAAIN tools? Visit gaaindata.org.

Email: info@GAAIN.org Website: http://www.gaain.org

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